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BACKGROUND: Improved technologies paired with an increase in access to genetic testing have led to the availability of expanded carrier screening evaluating hundreds of disorders. Currently, most autosomal dominant mutations, such as BRCA1, are not included in expanded carrier assays. Screening pregnant or preconception reproductive-aged women for BRCA1 may present a unique opportunity to perform population-based screening for patients at a time when precancer screening, chemoprevention, and/or risk-reducing surgery may be beneficial. OBJECTIVE: This study aimed to inform clinical decision-making as to whether the universal incorporation of BRCA1 testing at the time of obstetrical prenatal carrier screening is cost-effective. STUDY DESIGN: A decision analysis and Markov model was created. The initial decision point in the model was BRCA1 testing at the time of expanded carrier screening. Model probabilities, cost, and utility values were derived from published literature. For BRCA1-positive patients, the model simulated breast cancer screening and risk-reducing surgical interventions. A cycle length of 1 year and a time horizon of 47 years were used to simulate the lifespan of patients. The setting was obstetrical clinics in the United States, and the participants were a theoretical cohort of 1,429,074 pregnant patients who annually underwent expanded carrier screening. RESULTS: Among our cohort, BRCA1 testing resulted in the identification of an additional 3716 BRCA1-positive patients, the prevention of 1394 breast and ovarian cancer cases, and 1084 fewer deaths. BRCA1 testing was a cost-effective strategy compared with no BRCA1 testing with an incremental cost-effectiveness ratio of $86,001 per quality-adjusted life years. In a 1-way sensitivity analysis, we varied the prevalence of BRCA1 in the population from 0.00% to 20.00% and found that BRCA1 testing continued to be the cost-effective strategy until the prevalence rate was reduced to 0.16%. Multiple additional sensitivity analyses did not substantially affect the cost-effectiveness. CONCLUSION: The addition of BRCA1 testing to obstetrical prenatal carrier screening is a cost-effective management strategy to identify at-risk women at a time when cancer screening and preventive strategies can be effective. Despite the burden of additional genetic counseling, prenatal care represents a unique opportunity to implement population-based genetic testing.
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OBJECTIVE: To develop and evaluate a multidimensional comorbidity index (MCI) that identifies ovarian cancer patients at risk of early mortality more accurately than the Charlson Comorbidity Index (CCI) for use in health services research. METHODS: We utilized SEER-Medicare data to identify patients with stage IIIC and IV ovarian cancer, diagnosed in 2010-2015. We employed partial least squares regression, a supervised machine learning algorithm, to develop the MCI by extracting latent factors that optimally captured the variation in health insurance claims made in the year preceding cancer diagnosis, and 1-year mortality. We assessed the discrimination and calibration of the MCI for 1-year mortality and compared its performance to the commonly-used CCI. Finally, we evaluated the MCI's ability to reduce confounding in the association of neoadjuvant chemotherapy (NACT) and all-cause mortality. RESULTS: We included 4723 patients in the development cohort and 933 in the validation cohort. The MCI demonstrated good discrimination for 1-year mortality (c-index: 0.75, 95% CI: 0.72-0.79), while the CCI had poor discrimination (c-index: 0.59, 95% CI: 0.56-0.63). Calibration plots showed better agreement between predicted and observed 1-year mortality risk for the MCI compared with CCI. When comparing all-cause mortality between NACT with primary cytoreductive surgery, NACT was associated with a higher hazard of death (HR: 1.13, 95% CI: 1.04-1.23) after controlling for tumor characteristics, demographic factors, and the CCI. However, when controlling for the MCI instead of the CCI, there was no longer a significant difference (HR: 1.05, 95% CI: 0.96-1.14). CONCLUSIONS: The MCI outperformed the conventional CCI in predicting 1-year mortality, and reducing confounding due to differences in baseline health status in comparative effectiveness analysis of NACT versus primary surgery.
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Procedimentos Cirúrgicos de Citorredução , Aprendizado de Máquina , Terapia Neoadjuvante , Neoplasias Ovarianas , Programa de SEER , Humanos , Feminino , Procedimentos Cirúrgicos de Citorredução/métodos , Idoso , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Idoso de 80 Anos ou mais , Estados Unidos/epidemiologia , Quimioterapia Adjuvante , Viés , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/cirurgia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Estadiamento de Neoplasias , Medicare/estatística & dados numéricosRESUMO
OBJECTIVE: The recent Study 309-KEYNOTE-775 showed improved survival for lenvatinib plus pembrolizumab compared to chemotherapy in patients with recurrent endometrial cancer. We created a decision model to compare the cost-effectiveness of lenvatinib plus pembrolizumab in patients with recurrent mismatch repair-proficient (pMMR) endometrial cancer who had progressed after first-line chemotherapy. METHODS: A Markov model was created to simulate the clinical trajectory of 10,000 patients with recurrent pMMR endometrial cancer. The initial decision point in the model was treatment with ether lenvatinib plus pembrolizumab or chemotherapy (doxorubicin or dose-dense paclitaxel). Model probabilities, utility values and costs were derived with assumptions drawn from published literature. A cycle length of 3 months and a time horizon of 2 years was used. The effectiveness was calculated in terms of average quality adjusted life years (QALYs) gained. The primary outcome was incremental cost-effectiveness ratios (ICERs), expressed in 2020 US dollars/QALYs. One-way, two-way and probabilistic sensitivity analyses were performed. RESULTS: Chemotherapy was the least costly strategy at $66,693 followed by lenvatinib plus pembrolizumab ($193,590). Lenvatinib plus pembrolizumab resulted in more patients being alive at 2 years (lenvatinib plus pembrolizumab: 367, chemotherapy: 109). Chemotherapy was cost-effective compared with lenvatinib plus pembrolizumab (ICER: $164,493/QALYs). Lenvatinib plus pembrolizumab became cost-effective when its cost was reduced by $1553 per month (7.8% reduction). CONCLUSION: For patients with recurrent pMMR endometrial cancer Lenvatinib plus pembrolizumab is associated with greater survival but is more costly than chemotherapy. The cost of lenvatinib and pembrolizumab would have to be reduced by approximately 7% to be considered cost-effective.
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Anticorpos Monoclonais Humanizados , Reparo de Erro de Pareamento de DNA , Neoplasias do Endométrio , Compostos de Fenilureia , Quinolinas , Feminino , Humanos , Análise Custo-Benefício , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Anos de Vida Ajustados por Qualidade de VidaRESUMO
OBJECTIVE: To investigate associations between air particulate matter of ≤2.5 µm in diameter (PM2.5 ) and ovarian cancer. DESIGN: County-level ecological study. SETTING: Surveillance, epidemiology, and end results from a collection of state-level cancer registries across 744 counties. Data from the Environmental Protection Agency's network for PM2.5 monitoring was used to calculate trailing 5- and 10-year PM2.5 county-level values. County-level data on demographic characteristics were obtained from the American Community Survey. POPULATION: A total of 98 751 patients with histologically confirmed ovarian cancer as a primary malignancy from 2000 to 2016. METHODS: Generalised linear regression models were developed to estimate the association between PM2.5 and PM10 levels, over 5- and 10-year periods of exposure, and ovarian cancer risk, after accounting for county-level covariates. MAIN OUTCOME MEASURES: Risk ratios for associations between ovarian cancer (both overall and specifically epithelial ovarian cancer) and PM2.5 levels. RESULTS: For the 744 counties included, the average PM2.5 level from 1990 through 2018 was 11.75 µg/m3 (SD = 3.7) and the average PM10 level was 22.7 µg/m3 (SD = 5.7). After adjusting for county-level covariates, the overall annualised ovarian cancer incidence was significantly associated with increases in 5-year PM2.5 (RR = 1.11 per 10 units (µg/m3 ) increase, 95% CI 1.06-1.16). Similarly, when the analysis was limited to epithelial cell tumours and adjusted for county-level covariates there was a significant association with trailing 5-year PM2.5 exposure models (RR = 1.12 per 10 units increase, 95% CI 1.08-1.17). Likewise, 10-year PM2.5 exposure was associated with ovarian cancer overall and with epithelial ovarian cancer. CONCLUSIONS: Higher county-level ambient PM2.5 levels are associated with 5- and 10-year incidences of ovarian cancer, as measurable in an ecological study.
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Poluentes Atmosféricos , Poluição do Ar , Neoplasias Ovarianas , Humanos , Feminino , Material Particulado/efeitos adversos , Material Particulado/análise , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Incidência , Carcinoma Epitelial do Ovário/epidemiologia , Carcinoma Epitelial do Ovário/etiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Poluição do Ar/efeitos adversos , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/etiologiaRESUMO
OBJECTIVE: As the prognosis for endometrial cancer is excellent, management of the effects of estrogen deprivation has an important influence on quality of life. We examined the trends in the use of estrogen replacement therapy (ERT) and non-hormonal medications among patients with uterine cancer following surgery. METHODS: The MarketScan Database was used to identify patients 18-49 years who underwent hysterectomy plus oophorectomy and those aged 50-75 years who underwent hysterectomy between 2008 and 2020. ERT and non-hormonal treatments of menopause were identified preoperatively and postoperatively. After propensity score balancing, difference-in-differences (DID) analyses were performed to compare the pre-and-postoperative changes in ERT and non-hormonal medication use between groups. The trends in postoperative use of ERT were assessed and tested using Cochran-Armitage trend tests. RESULTS: A total of 19,700 patients with uterine cancer and 185,150 controls were identified. Overall, postoperative ERT use decreased for both age groups and for patients with and without uterine cancer. The DID in ERT use between those with uterine cancer and those with benign pathology after hysterectomy was -37.1% (95% CI, -40.5 to -33.6%) for patients 18-49 years of age and - 10.4% (95% CI, -10.9 to -9.9%) for those 50-75 years. The DID for non-hormonal medication use between those with uterine cancer and those with benign pathology after hysterectomy was 11.2% (95% CI, 7.8 to 14.7%) for younger patients and 3.4% (95% CI, 2.9 to 4.0%) for those 50-75 years. The postoperative new ERT use has been declining over time in patients with uterine cancer in those 18-49 years of age (P = .02) and those 50-75 years of age (P < .001). CONCLUSIONS: The use of ERT is uncommon and has declined over time in patients with uterine cancer. Conversely, non-hormonal medications are more commonly used among patients with uterine cancer.
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Terapia de Reposição de Estrogênios , Neoplasias Uterinas , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Qualidade de Vida , Menopausa , Estrogênios , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/cirurgiaRESUMO
OBJECTIVE: To evaluate the association between hospital volume and the quality of gynecologic emergency care for tubal ectopic pregnancies, ovarian torsion, and pelvic inflammatory disease (PID). METHODS: In this cross-sectional analysis, we analyzed patients who presented for emergency care for tubal ectopic pregnancies, ovarian torsion, and PID using the Premier Healthcare Database from 2006 to 2020. We measured the following outcomes: methotrexate use for ectopic pregnancy, ovarian cystectomy for torsion, and guideline-based antibiotic use for PID. For each condition, we measured outlier hospitals that performed the above interventions at below the 10th percentile. Multivariable logistic regression models were used to analyze associations between outlier care and hospital factors such as annualized mean case volume, urban or rural location, teaching status, bed capacity, and geographic region, as well as hospital-level patient population factors, including age, insurance status, and race. RESULTS: A total of 602 hospitals treated patients with tubal ectopic pregnancies, of which 21.9% were outliers, with no cases managed with methotrexate. Of 512 hospitals treating patients with ovarian torsion, 17.4% were outliers, with no cases managed with cystectomy. Of 929 hospitals that treated patients with PID, 9.9% were deemed outliers with low rates of guideline-adherent antibiotic administration. Low-volume hospitals were more likely to be outliers with low rates of use of methotrexate for ectopic pregnancy (6.7% of high-volume hospitals vs 49.7% of low-volume hospitals were outliers; adjusted odds ratio [aOR] 0.13, 95% CI, 0.05-0.31 for high-volume hospitals) and cystectomy for torsion (34.9% of low-volume vs 2.4% of high-volume hospitals were outliers; aOR 0.05, 95% CI, 0.01-0.18 for high-volume hospitals). There was no association between hospital volume and lower rates of guideline-based antibiotic use for PID. CONCLUSION: Higher hospital volume is associated with use of conservative, fertility-preserving treatment of emergency gynecologic conditions, including ectopic pregnancy and ovarian torsion.
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Serviços Médicos de Emergência , Doença Inflamatória Pélvica , Gravidez Ectópica , Gravidez Ovariana , Gravidez Tubária , Gravidez , Humanos , Feminino , Metotrexato , Torção Ovariana/complicações , Estudos Transversais , Gravidez Ectópica/cirurgia , Hospitais com Alto Volume de Atendimentos , Antibacterianos/uso terapêuticoRESUMO
INTRODUCTION: Little is known as to how prolonged screening recommendations for cervical cancer have affected compliance. OBJECTIVE: We examined compliance with repeat cervical cancer screening among U.S. women aged 30-64 who underwent index screening between 2013 and 2019. STUDY DESIGN: The IBM Watson Health MarketScan Database was used to identify commercially-insured women 30-64 years old who underwent cervical cancer screening from 2013 to 2019. The cohort was limited to women with continuous insurance 12 months before and ≥ 2 months after index testing. Patients with prior hysterectomy, more frequent surveillance needs, or a history of abnormal cytology, histology, or HPV test were excluded. Index screening included cytology, co-testing, or primary HPV testing. Cumulative incidence curves described screening intervals. Compliance was considered if repeat screening occurred 2.5-4 years after index cytology and 4.5-6 years after index co-testing. Cause-specific hazard models examined factors associated with compliance. RESULTS: Of 5,368,713 patients identified, co-testing was performed in 2,873,070 (53.5%), cytology in 2,422,480 (45.1%), and primary HPV testing in 73,163 (1.4%). The cumulative incidence of repeat screening among all women by seven years was 81.9%. Of those who underwent repeat screening, 85.7% with index cytology and 96.6% with index co-testing were rescreened early. Only, 12.2% with index cytology had appropriate rescreening and 2.1% had delayed rescreening. Among the index co-testing group, 3.2% had appropriate rescreening and 0.3% had delayed rescreening. CONCLUSION: Appropriate cervical cancer follow-up screening is highly variable. The cumulative incidence rate of repeat screening was 81.9% and among women rescreened, the vast majority are tested earlier than recommended by current guidelines.
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Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Seguimentos , Detecção Precoce de Câncer , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/complicações , Programas de Rastreamento , Esfregaço Vaginal , PapillomaviridaeRESUMO
OBJECTIVE: Oral tyrosine kinase inhibitors (TKIs) have new indications for treatment in gynecologic malignancies. These targeted drugs have both unique and overlapping toxicities, which require careful attention and management. New combination therapies with immune-oncology agents have demonstrated promise in endometrial cancer. This review examines common adverse events associated with TKIs and provides readers with an evidence-based review on current uses and strategies for the management of these medications. METHODS: A comprehensive review of the medical literature on TKI use in gynecologic cancer was undertaken by a committee approach. Details of each drug, its molecular target, and relevant data on both clinical efficacy and side effects were compiled and organized for clinical use. Information on drug-related secondary effects and management strategies for specific toxicities, including dose reduction and concomitant medications, were gathered. RESULTS: TKIs can potentially offer improved response rates and durable responses for a group of patients who were previously without an effective standard second-line therapy. The combination of lenvatinib and pembrolizumab represents a more targeted approach to the drivers of endometrial cancer; however, there remains significant drug-related toxicity, and thus dose reduction and dose delay are frequently required. Toxicity management requires frequent check-ins and management strategies to help patients find the highest tolerable dose. TKIs are expensive and patient financial toxicity is as critical a measure of a drug's utility as any drug side effect. Many of these drugs have patient assistance programs, which should be fully utilized to minimize cost. CONCLUSIONS: Future studies are needed to expand the role of TKIs into new molecularly driven groups. Attention to cost, durability of response, and long-term toxicity management is needed to ensure all eligible patients have access to treatment.
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Antineoplásicos , Neoplasias do Endométrio , Feminino , Humanos , Antineoplásicos/efeitos adversos , Neoplasias do Endométrio/tratamento farmacológico , Resultado do Tratamento , /efeitos adversosRESUMO
OBJECTIVE: To estimate trends in use and outcomes of progestin therapy for premenopausal patients with endometrial intraepithelial neoplasia. METHODS: The MarketScan Database was used to identify patients aged 18-50 years with endometrial intraepithelial neoplasia from 2008 to 2020. Primary treatment was classified as hysterectomy or progestin-based therapy. Within the progestin group, treatment was classified as systemic therapy or progestin-releasing intrauterine device (IUD). The trends in use of progestins and the pattern of progestin use were examined. A multivariable logistic regression model was fit to examine the association between baseline characteristics and the use of progestins. The cumulative incidence of hysterectomy, uterine cancer, and pregnancy since initiation of progestin therapy was analyzed. RESULTS: A total of 3,947 patients were identified. Hysterectomy was performed in 2,149 (54.4%); progestins were used in 1,798 (45.6%). Use of progestins increased from 44.2% in 2008 to 63.4% in 2020 ( P =.002). Among the progestin users, 1,530 (85.1%) were treated with systemic progestin, and 268 (14.9%) were treated with progestin-releasing IUD. Among progestin users, use of IUD increased from 7.7% in 2008 to 35.6% in 2020 ( P <.001). Hysterectomy was ultimately performed in 36.0% (95% CI 32.8-39.3%) of those who received systemic progestins compared with 22.9% (95% CI 16.5-30.0%) of those treated with progestin-releasing IUD ( P <.001). Subsequent uterine cancer was documented in 10.5% (95% CI 7.6-13.8%) of those who received systemic progestins compared with 8.2% (95% CI 3.1-16.6%) of those treated with progestin-releasing IUD ( P =.24). Venous thromboembolic complications occurred in 27 (1.5%) of those treated with progestins; the venous thromboembolism (VTE) rate was similar for oral progestins and progestin-releasing IUD. CONCLUSION: The rate of conservative treatment with progestins in premenopausal individuals with endometrial intraepithelial neoplasia has increased over time, and among progestin users, progestin-releasing IUD use is increasing. Progestin-releasing IUD use may be associated with a lower rate of hysterectomy and a similar rate of VTE compared with oral progestin therapy.
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Hiperplasia Endometrial , Dispositivos Intrauterinos Medicados , Dispositivos Intrauterinos , Neoplasias Uterinas , Tromboembolia Venosa , Gravidez , Feminino , Humanos , Progestinas/uso terapêutico , Levanogestrel/uso terapêutico , Tromboembolia Venosa/etiologia , Hiperplasia Endometrial/etiologia , Neoplasias Uterinas/etiologia , Dispositivos Intrauterinos Medicados/efeitos adversosRESUMO
Predicting in vivo response to antineoplastics remains an elusive challenge. We performed a first-of-kind evaluation of two transcriptome-based precision cancer medicine methodologies to predict tumor sensitivity to a comprehensive repertoire of clinically relevant oncology drugs, whose mechanism of action we experimentally assessed in cognate cell lines. We enrolled patients with histologically distinct, poor-prognosis malignancies who had progressed on multiple therapies, and developed low-passage, patient-derived xenograft models that were used to validate 35 patient-specific drug predictions. Both OncoTarget, which identifies high-affinity inhibitors of individual master regulator (MR) proteins, and OncoTreat, which identifies drugs that invert the transcriptional activity of hyperconnected MR modules, produced highly significant 30-day disease control rates (68% and 91%, respectively). Moreover, of 18 OncoTreat-predicted drugs, 15 induced the predicted MR-module activity inversion in vivo. Predicted drugs significantly outperformed antineoplastic drugs selected as unpredicted controls, suggesting these methods may substantively complement existing precision cancer medicine approaches, as also illustrated by a case study. SIGNIFICANCE: Complementary precision cancer medicine paradigms are needed to broaden the clinical benefit realized through genetic profiling and immunotherapy. In this first-in-class application, we introduce two transcriptome-based tumor-agnostic systems biology tools to predict drug response in vivo. OncoTarget and OncoTreat are scalable for the design of basket and umbrella clinical trials. This article is highlighted in the In This Issue feature, p. 1275.
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Antineoplásicos , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Transcriptoma , Medicina de Precisão/métodos , Oncologia/métodos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêuticoRESUMO
OBJECTIVE: Patients with recurrent endometrial cancer treated with carboplatin and paclitaxel whose disease progresses have few effective treatment options. Based on promising clinical trial data, the anti-programmed cell death 1 (anti-PD-1) antibody dostarlimab was recently granted accelerated approval for endometrial cancer by the US Food and Drug Administration. We developed a decision model to examine the cost-effectiveness of dostarlimab for patients with progressive/recurrent deficient mismatch repair (dMMR) endometrial cancer whose disease has progressed with first-line chemotherapy. DESIGN: Cost-effectiveness study. POPULATION: Hypothetical cohort of 6000 women with progressive/recurrent dMMR endometrial cancer. METHODS: The initial decision point in the Markov model was treatment with dostarlimab, pembrolizumab or pegylated liposomal doxorubicin (PLD). Model probabilities, and cost and utility values were derived with assumptions drawn from published literature. Effectiveness was estimated as average quality-adjusted life years (QALYs) gained. One-way, two-way and probabilistic sensitivity analyses were performed to vary the assumptions across a range of plausible values. MAIN OUTCOME MEASURES: The primary outcome was the incremental cost-effectiveness ratio (ICER). RESULTS: Pegylated liposomal doxorubicin (PLD) was the least costly strategy, at $55,732, followed by dostarlimab ($151,533) and pembrolizumab ($154,597). Based on a willingness-to-pay threshold of $100,000/QALY, PLD was cost-effective compared with dostarlimab, with an ICER of $331,913 per QALY gained for dostarlimab, whereas pembrolizumab was ruled out by extended dominance (less effective, more costly), compared with dostarlimab. In one-way sensitivity analyses, dostarlimab was cost-effective when its cost was reduced to $4905 (52% reduction). These results were robust in a variety of sensitivity analyses. CONCLUSIONS: Dostarlimab is associated with greater survival compared with other treatments for women with recurrent dMMR endometrial cancer. Although the agent is substantially more costly, dostarlimab became cost-effective when its cost was reduced to $5489 per cycle.
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Reparo de Erro de Pareamento de DNA , Neoplasias do Endométrio , Humanos , Feminino , Análise Custo-Benefício , Recidiva Local de Neoplasia/tratamento farmacológico , Anos de Vida Ajustados por Qualidade de Vida , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genéticaRESUMO
OBJECTIVE: To assess heterogeneity in five-year overall survival of patients with endometrial cancer using a large retrospective database with cohorts defined by recent prospective clinical trials. METHODS: The National Cancer Database was used to identify patients with endometrial cancer who underwent hysterectomy from 2004 to 2016. The reported inclusion criteria for GOG-249, PORTEC-3, and GOG-258 were used to define the respective cohorts. Five-year overall survival for each cohort was stratified by tumor characteristics and adjuvant therapy regimens. RESULTS: A total of 89,133 patients were identified who would have fulfilled the entry criteria to GOG-249, PORTEC-3, or GOG-258. When stratified by tumor characteristics, irrespective of adjuvant therapy, five-year overall survival ranged from 59.9%-81.7% for patients meeting GOG-249 inclusion criteria, 40.2%-81.8% for patients meeting PORTEC-3 inclusion criteria, and 17.5%-75.0% for those meeting GOG-258 inclusion criteria. Analysis of subgroups by adjuvant therapy regimen revealed significant improvement in five-year overall survival for chemoradiotherapy compared to chemotherapy or radiotherapy alone for endometroid stage III and stage IVA disease and for some stages of serous and clear cell histology. CONCLUSIONS: Recent prospective trials of adjuvant therapy for endometrial cancer have included heterogeneous cohorts of patients based on five-year overall survival rates when the populations are stratified by tumor characteristics. The variation in expected five-year overall survival for subsets of patients may result in underpowered studies or misleading results.
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Neoplasias do Endométrio , Feminino , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Radioterapia Adjuvante , Estadiamento de Neoplasias , Neoplasias do Endométrio/patologia , Histerectomia , Quimioterapia AdjuvanteRESUMO
OBJECTIVE: Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. We examined the utility of circulating tumor DNA (ctDNA) as a prognostic biomarker for EOC by assessing its relationship with patient outcome and CA-125, pre-surgically and during post-treatment surveillance. METHODS: Plasma samples were collected from patients with stage I-IV EOC. Cohort A included patients with pre-surgical samples (N = 44, median follow-up: 2.7 years), cohort B and C included: patients with serially collected post-surgically (N = 12) and, during surveillance (N = 13), respectively (median follow-up: 2 years). Plasma samples were analyzed using a tumor-informed, personalized multiplex-PCR NGS assay; ctDNA status and CA-125 levels were correlated with clinical features and outcomes. RESULTS: Genomic profiling was performed on the entire cohort and was consistent with that seen in TCGA. In cohort A, ctDNA-positivity was observed in 73% (32/44) of presurgical samples and was higher in high nuclear grade disease. In cohort B and C, ctDNA was only detected in patients who relapsed (100% sensitivity and specificity) and preceded radiological findings by an average of 10 months. The presence of ctDNA at a single timepoint after completion of surgery +/- adjuvant chemotherapy and serially during surveillance was a strong predictor of relapse (HR:17.6, p = 0.001 and p < 0.0001, respectively), while CA-125 positivity was not (p = 0.113 and p = 0.056). CONCLUSIONS: The presence of ctDNA post-surgically is highly prognostic of reduced recurrence-free survival. CtDNA outperformed CA-125 in identifying patients at highest risk of recurrence. These results suggest that monitoring ctDNA could be beneficial in clinical decision-making for EOC patients.
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DNA Tumoral Circulante , Neoplasias Ovarianas , Humanos , Feminino , DNA Tumoral Circulante/genética , Carcinoma Epitelial do Ovário , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/cirurgia , Biomarcadores Tumorais/genética , MutaçãoRESUMO
OBJECTIVE: To estimate trends in use of laparoscopic power morcellators in women undergoing minimally invasive hysterectomy and to examine use of containment systems in these patients in relation to safety guidance from the U.S. Food and Drug Administration (FDA). METHODS: We examined data that were recorded in the Premier Healthcare Database from patients who underwent laparoscopic supracervical hysterectomy from 2010 to 2018. Patients were stratified based on use of laparoscopic power morcellators. The cohort was further stratified as either pre-FDA guidance (2010 quarter 1-2014 quarter 1) or post-FDA guidance (2014 quarter 2-2018 quarter 2). Interrupted time series analyses were performed to determine the effect of FDA guidance on the use of laparoscopic power morcellators and containment bags. RESULTS: Among 67,115 patients, laparoscopic power morcellator use decreased from 66.7% in 2013 quarter 4 to 13.3% by 2018 quarter 2. The likelihood of laparoscopic power morcellator use decreased by 9.5% for each quarter elapsed in the post-FDA warning period (risk ratio [RR] 0.91, 95% CI 0.90-0.91). Containment bag use rose from 5.2% in 2013 quarter 4 to 15.2% by 2018 quarter 2. The likelihood of containment bag use increased by 3% for each quarter elapsed in the post-FDA warning period (RR 1.03, 95% CI 1.02-1.05). Among women who had laparoscopic power morcellator use, uterine cancers or sarcomas were identified in 54 (0.17%) before the FDA guidance compared with seven (0.12%) after the guidance ( P =.45). Containment bags were used in 11.1% of women with uterine cancers or sarcomas before the FDA guidance compared with 14.3% after the guidance ( P =.12). The perioperative complication rate was 3.3% among women who had laparoscopic power morcellator use without a containment bag compared with 4.5% ( P =.001) in those with a containment bag (aRR 1.35, 95% CI 1.12-1.64). CONCLUSION: Use of laparoscopic power morcellators has decreased over time. Containment bag use increased after the FDA's 2014 guidance; however, most procedures employing laparoscopic power morcellators are still performed without a containment bag.
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Laparoscopia , Morcelação , Sarcoma , Miomectomia Uterina , Neoplasias Uterinas , Humanos , Feminino , Morcelação/efeitos adversos , Histerectomia/métodos , Neoplasias Uterinas/cirurgia , Laparoscopia/efeitos adversos , Sarcoma/etiologia , Sarcoma/cirurgia , Miomectomia Uterina/métodosRESUMO
OBJECTIVE: To examine temporal trends in cervical cancer screening practices and associated downstream abnormalities and procedures. METHODS: Women aged 18-64 years with commercial insurance or Medicaid insurance from 2008 to 2019 were identified using the IBM MarketScan databases. The annual rates of screening overall and by type of test (cytology, co-testing, or primary human papillomavirus testing) were examined. Downstream abnormal cytologic and histologic test results, colposcopies, and excisional procedures were examined, and rates were reported for the population of eligible patients with continuous insurance and for those who underwent screening. Changes over time in testing and outcomes were compared using χ2 tests and Spearman's correlation. RESULTS: From 2008 to 2019, the annual screening prevalence decreased from 42.6% to 29.4% in women with commercial insurance (P<.001) and from 27.9% to 12.4% among women with Medicaid insurance (P<.001). In the cohort of women with commercial insurance, cytology usage decreased from 79.4% to 38.9% and co-testing increased from 20.1% to 59.6% (P<.001). Per 1,000 women screened, the rate of abnormal histologic and cytologic test results rose from 96 to 119 (P<.001) and colposcopies rose from 33 to 42 (P<.001); excisional procedures remained relatively constant. Per 1,000 eligible women, the rate of abnormal histologic and cytologic test results decreased from 41 to 35 (P<.001), colposcopies declined from 14 to 12, and excisional procedures decreased from 3 to 2. CONCLUSION: Human papillomavirus testing has been rapidly incorporated into cervical cancer screening and is associated with an increasing trend of downstream abnormalities and procedures among screened women but a declining trend at the population level.
Assuntos
Seguro , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Colposcopia , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Programas de Rastreamento/métodos , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Gravidez , Estados Unidos , Neoplasias do Colo do Útero/patologiaRESUMO
OBJECTIVE: Preclinical evidence and early clinical trials have demonstrated the activity of SPL-108, a targeted agent that inhibits CD44 mediated induction of multidrug resistance specifically to paclitaxel and platinum agents. We conducted a phase I, open label, dose escalation study of the safety and tolerability of the combination of SPL-108 with weekly paclitaxel in patients with platinum resistant CD44+ ovarian, primary peritoneal, or fallopian tube cancer. METHODS: Patients with platinum resistant histologically proven epithelial ovarian, primary peritoneal, or fallopian tube cancers and measurable disease according to RECIST (Response Evaluation Criteria in Solid Tumours) version 1.1 were selected. Tumors were tested for CD44 expression for eligibility, defined as strong (+++) or moderate (++) staining in ≥20% of the tumor tissue or diffuse + staining. Patients were treated with daily and then twice daily SPL-108 subcutaneous injections and weekly intravenous paclitaxel on days 1, 8, and 15 of a 28 day cycle. Endpoints included safety, determination of maximum tolerated dose, and efficacy. Tumors underwent comprehensive genomic profiling, and cell lines and western blotting were used to study markers of response. RESULTS: We screened 16 patients, and 14 were enrolled based on CD44+ expression. A total of 86% of patients had high grade serous tumors and all had received multiple prior therapies. There were no grade 4-5 toxicities. One patient had grade 3 peripheral sensory neuropathy attributed to paclitaxel and one patient developed presumed colonic perforation attributed to the study drug. No dose reductions or treatment discontinuations were required. All patients tolerated the maximum planned dose; no maximum tolerated dose was reached. Overall response rate was 36%; 5 (36%) patients had partial response and 5 (36%) patients had stable disease. CONCLUSIONS: The combination of SPL-108 with weekly paclitaxel was safe and well tolerated. Encouraging antitumor activity was observed, with 72% of patients deriving a clinical benefit. TRIAL REGISTRATION: NCT03078400.
RESUMO
OBJECTIVES: The optimal adjuvant therapy for uterine leiomyosarcoma (uLMS) remains uncertain. We analyzed the utilization of adjuvant chemotherapy and radiation therapy for stage II and III uLMS and explored the association between use of adjuvant therapy and survival. METHODS: Patients with stage II or III uLMS treated from 2004 to 2016 and recorded in the National Cancer Database were identified. Multivariable regression models were fit to estimate predictors of use of either adjuvant radiation therapy or chemotherapy. To analyze the impact of chemotherapy on all-cause mortality, an inverse probability of treatment weighted (IPTW) propensity score method was used to account for measured confounders, and the receipt of radiation therapy was adjusted in the outcome model. The process was repeated to analyze the impact of radiation therapy on all-cause mortality by using an IPTW propensity score method and adjusting for the receipt of adjuvant chemotherapy. RESULTS: A total of 890 patients were identified. Adjuvant chemotherapy use increased from 62.2% in 2010 to 70.4% in 2016, whereas radiation usage decreased from 26.7% in 2010 to 10.4% in 2016. Patients with stage III (vs. stage II) disease were less likely to receive radiation therapy. After propensity score weighting, chemotherapy was associated with a 30% decreased risk of all-cause mortality in stage III patients (HR 0.70, 95% CI 0.45-0.98) but had no effect on mortality for stage II patients (HR 0.93, 95% CI 0.70-1.20). Radiation therapy was associated with a 26% decreased risk of mortality for stage II tumors (HR 0.74; 95% CI, 0.53-0.99) and a 57% decrease in mortality for stage III disease (HR 0.43, 95% CI 0.18-0.99). CONCLUSIONS: Among women with stage II-III uLMS, use of chemotherapy is increasing while use of radiation therapy is decreasing. Radiation therapy is associated with improved survival in both stage II and III disease, while there was no association between use of adjuvant chemotherapy and survival in stage II patients.
Assuntos
Quimioterapia Adjuvante , Leiomiossarcoma , Neoplasias Pélvicas , Neoplasias Uterinas , Quimioterapia Adjuvante/métodos , Terapia Combinada , Feminino , Humanos , Leiomiossarcoma/patologia , Leiomiossarcoma/terapia , Estadiamento de Neoplasias , Neoplasias Pélvicas/patologia , Neoplasias Pélvicas/terapia , Radioterapia Adjuvante/métodos , Estudos Retrospectivos , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapiaRESUMO
OBJECTIVE: To examine the use of estrogen therapy (ET) and patterns of follow-up evaluation for sequelae of estrogen deprivation among women who were premenopausal who underwent bilateral salpingo-oophorectomy (BSO) for benign gynecologic diseases. METHODS: The IBM Watson Health MarketScan Research Databases were used to identify women between age 18 and 50 years who underwent BSO from 2008 to 2019. Estrogen therapy was defined as any prescription of estrogen filled from 6 weeks before BSO to 36 months after BSO. Patterns of follow-up testing including bone mineral density and lipid testing were examined. RESULTS: We identified a total of 61,980 women who underwent BSO for benign indications. Overall, 64.5% (95% CI 64.1-64.9%) of women received ET. The rate of ET use within 36 months of surgery declined from a peak of 69.5% in 2008 to 58.2% in 2016. The median duration of continuous ET was 5.3 months. Estrogen therapy use declined with increasing age. The cumulative rate of ET use at 36 months after surgery was 79.1% (95% CI 76.9-81.1) in those aged 18-29 years, 75.9% (95% CI 74.5-77.3%) in those aged 30-34 years, 70.2% (95% CI 69.1-71.2%) in those aged 35-39 years, 66.1% (95% CI 65.3-66.9%) in those aged 40-44 years, and 60.0% (95% CI 59.4-60.6%) in those aged 45-50 years. In a multivariable model, women who underwent surgery more recently and those with medical comorbidities were less likely to receive ET, whereas younger women, those with Medicaid insurance, those outside of the northeast, and those who underwent concurrent hysterectomy were more likely to receive ET. CONCLUSION: Estrogen therapy use in women who are premenopausal who underwent BSO for benign gynecologic diseases has declined substantially over the past decade.
Assuntos
Doenças dos Genitais Femininos , Salpingo-Ooforectomia , Estrogênios/uso terapêutico , Feminino , Humanos , Histerectomia , Ovariectomia , Pré-Menopausa , SíndromeRESUMO
BACKGROUND: The utility of prophylactic endovascular internal iliac balloon placement in the surgical management of placenta accreta spectrum is debated. OBJECTIVE: In this study, we review outcomes of surgical management of placenta accreta spectrum with and without prophylactic endovascular internal iliac balloon catheter use at a single institution. STUDY DESIGN: This is a retrospective cohort study of consecutive viable singleton pregnancies with a confirmed pathologic diagnosis of placenta accreta spectrum undergoing scheduled delivery from October 2018 through November 2020. In the T1 period (October 2018-August 2019), prophylactic endovascular internal iliac balloon catheters were placed in the operating room before the start of surgery. Balloons were inflated after neonatal delivery and deflated after hysterectomy completion. In the T2 period (September 2019-November 2020), endovascular catheters were not used. In both time periods, all surgeries were performed by a dedicated multidisciplinary team using a standardized surgical approach. The outcomes compared included the estimated blood loss, anesthesia duration, operating room time, surgical duration, and a composite of surgical complications. Comparisons were made using the Wilcoxon rank-sum test and the Fisher exact test. RESULTS: A total of 30 patients were included in the study (T1=10; T2=20). The proportion of patients with placenta increta or percreta was 80% in both groups, as defined by surgical pathology. The median estimated blood loss was 875 mL in T1 and 1000 mL in T2 (P=.84). The proportion of patients requiring any packed red blood cell transfusion was 60% in T1 and 40% in T2 (P=.44). The proportion of patients requiring >4 units of packed red blood cells was 20% in T1 and 5% in T2 (P=.25). Surgical complications were observed in 1 patient in each group. Median operative anesthesia duration was 497 minutes in T1 and 296 minutes in T2 (P<.001). Median duration of operating room time was 498 minutes in T1 and 205 minutes in T2 (P<.001). Median surgical duration was 227 minutes in T1 and 182 minutes in T2 (P<.05). The median duration of time for prophylactic balloon catheter placement was 74 minutes (range, 46-109 minutes). The median postoperative length of stay was similar in both groups (6 days in T1 and 5.5 days in T2; P=.36). CONCLUSION: The use of prophylactic endovascular internal iliac balloon catheters was not associated with decreased blood loss, packed red blood cell transfusion, or surgical complications. Catheter use was associated with increased duration of anesthesia, operating room time, and surgical time.